System for marking a location for treatment within the gastrointestinal tract

ABSTRACT

A device and method for mapping, diagnosing and treating the intestinal tract is provided using a capsule passing through the intestinal tract. Further, a capsule tracking system is provided for tracking a capsule&#39;s location along the length of an intestinal tract as various treatment and/or sensing modalities are employed. In one variation, an acoustic signal is used to determine the location of the capsule. A map of sensed information may be derived from the pass of a capsule. Capsules may be subsequently passed through to treat the intestinal tract at a determined location along its length. One variation uses an electrical stimulation capsule to treat and/or diagnose a condition in the intestinal tract.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/427,672 filed May 1, 2003 now U.S. Pat. No. 7,824,347 which is acontinuation of U.S. application Ser. No. 09/892,404 filed Jun. 26, 2001and issued as U.S. Pat. No. 7,160,258 on Jan. 9, 2007; both of theaforementioned priority applications are hereby incorporated herein byreference in their entirety.

FIELD OF THE INVENTION

This invention relates to a device and method for mapping, diagnosingand treating the intestinal tract using a capsule passing through theintestinal tract. Further, this invention relates to a capsule trackingsystem for tracking a capsule's location, including for tracking acorresponding diagnosis or treatment, along the length of an intestinaltract. The invention also relates to various treatment and diagnosismethods and devices that may be used with such a capsule and in such atracking system. One of such devices and methods concerns influencingand/or measuring the electrical behavior of the intestinal tract.

BACKGROUND OF THE INVENTION

Different areas of the intestinal tract have varying degrees of surgicalaccessibility. For example, there has been great difficulty indiagnosing and treating disorders in the human small intestine becauseof the length of the small intestine (typically about 21 feet or 7meters), and its inaccessibility. Also certain regions of the colon haveproven difficult to access for treatment. Accordingly, it would bedesirable to provide a less or minimally invasive device for diagnosingor treating difficult to access portions of the intestinal tract, suchas, the small intestine and colon.

Swallowable telemetry capsules have been used in a number of treatmentand diagnostic applications. Some swallowable capsules have beenproposed to deliver medication to specific areas of the intestinal tractwhere the release of the medication is actuated by an external RF signalreceived by the capsule. The signal actuates an electromechanical devicewithin the capsule to release the medication. Similarly, some capsuleshave been proposed to acquire samples from the intestinal tract whereactuation of an electromechanical sampling device is remotely controlledand the capsule is then retrieved when excreted. Other capsules havebeen proposed, for example, to take pictures or video images, or measurepH, pressure or temperature. An autonomous capsule with electrodes hasbeen proposed to provide electrical stimulation while moving through theGI tract to restore motor evacutory function of the GI tract. Such adevice has been proposed to propel a capsule through the gut.

Telemetry treatment and/or diagnostic capsules with mapping capabilitieshave been proposed to identify a target treatment site on athree-dimensional map of the intestinal tract. Generally, the proposedsystems include capsules that transmit RF signals to externally locatedantennas. The relative amplitudes of the RF signals received by theantennas are used to determine relative location of the capsule based onthe correlation between the capsule to antenna distance and RF amplitude(signal strength). According to these proposed systems, using four ormore antennas and triangulation techniques, the location of the capsulein two or three-dimensional space is determined based on RF amplitude.From the location information, a map of the capsule's path in space maybe created. In subsequent passes of the capsule through the intestinaltract, the capsule is used for treatment or diagnosis purposes at atarget location. In addition, it has been proposed to use video imagesin combination with such RF determined spatial information to identify atarget location in first and subsequent capsule passes.

A capsule with a mechanical cogwheel has been proposed to calculate thesmall bowel length and small bowel transit velocity. The device relieson the turning of the cogwheel by contact with the intestinal wallduring small bowel transit to calculate centimeters of travel.

Many disadvantages are inherent in the current capsule trackingtechniques. Tracking systems using RF amplitude data from signalstransmitted through body tissue have a high degree of error andinadequate resolution for accurate intestinal tract mapping. (With 1 cmintestinal diameters and substantial overlap of intestines, an accurateresolution is necessary.) The resolution problems are due to a number ofpossible inaccuracies, which are compounded because RF signal strengthover distance varies in a non-linear fashion. RF signal is directional,and thus its strength varies with the direction of the signal or theorientation of the coil transmitter with respect to the fixed coilreceiver. Thus, without any change in location, a change in orientationmay cause a dramatic change in RF amplitude at the antenna. Further, RFtransmission is absorbed by tissue, particularly at higher frequencies.Thus the larger coils that would be required to transmit lower frequencyRF signals, constrain the ability to miniaturize an optimal device.

In addition to RF resolution issues, due to movement and shifting of theintestinal organs within the abdomen, 3D mapping may not repeatablyidentify a precise location within the intestines when a subsequentcapsule is passed through the tract. The intestinal organs tend to shiftwith the filling or emptying of the various portions of the digestivesystem, and they tend to move with peristalsis. A patient's abdomen alsomoves with respiration and change in patient position. Thus, given theintestinal shifting along with the intestine's small diameter andoverlap, the 3D tracking system may identify the wrong portion of theintestinal tract when a later capsule passes through. Therefore, itwould be desirable to provide a tracking system that accurately andrepeatably identifies a desired location in the intestinal tract so thata location identified by a first capsule is substantially the same as alocation identified by a subsequently passed capsule. It would also bedesirable to provide a capsule and tracking system that does not rely onRF transmission amplitude data for accurate tracking.

As noted above, telemetry capsules have been used in therapeutic anddiagnostic applications. Such therapeutic and diagnostic devices havetypically involved providing medication to a location in the intestinaltract alone or in combination with sampling the fluids of the intestinaltract. The pH, temperature and pressure have also been measured. Itwould be desirable to provide capsules with new diagnostic and treatmentmodalities, particularly in a manner that would combine the treatmentwith tracking and diagnostic capabilities, to treat difficult to accessregions of the intestinal tract.

One clinically significant condition that has been challenging to treatin the intestines is bleeding. Location of bleeding in the intestinaltract is very difficult to identify and requires surgical interventionto correct if it persists. Therefore, it would be desirable to provide amethod and device for identifying a location of intestinal bleeding andfor treating the location in a less invasive manner.

Another diagnostic/therapeutic area of interest is in identifyingblockages or other diseased portions of the intestine and the ability tobiopsy the specific location where there is such a blockage or disease.It would also be of interest to assist a surgeon in specifically markinga site for surgery prior to surgical intervention for easieridentification of the site.

Another clinically significant parameter is the transit time ofmaterials through the intestines. Current techniques in measuringtransit time involve ingesting a material that reacts with the contentsof the colon such that the patient's breath gives off a detectable gasat such time. This technique is not very precise and does not provideinformation on, e.g., which particular portion of the tract isresponsible for transit abnormalities. Some patients have segmentaldiseases where a segment of the intestine does not have adequatemotility. Thus, velocity of travel of materials through various portionsof the intestine would be of interest in determining where there may besegmental disease.

Motility disorders in some situations relate to abnormalities in theperiodic, coordinated contractile activity of the smooth musclesassociated with the intestinal tract. Various organs of the intestinaltract such as the stomach, small intestine and colon contain cells thatare believed to govern the organs' periodic contractile behavior. Inhealthy humans, in certain intestinal tract regions, these cellsgenerate and propagate rhythmic electrical signals. In general, severaltypes of electrical potential activities have been observed in theintestinal tract. Consistent slow wave or pacesetter potentials havebeen observed and higher frequency spike activity has been observed. Thepacesetter potentials are continuously propagating, relatively lowfrequency, cyclic depolarizations of the smooth muscle lining. Thehigher frequency spike bursts tend to correspond with smooth musclecontractile activity including segmentation and peristalsis. In general,when the spike burst activity occurs, it appears to be at a fixed timedelay with respect to the slow wave potentials. It is believed that whenthe pacesetter potentials are combined with a chemical or neuralexcitation of the cells, smooth muscle contractile activity may occurand that the pacesetter potentials control and coordinate the frequencyand direction of the contractions.

Accordingly, it would be of interest to provide a means for observingthe electrical activity such as, for example, the vagal nerve activity,the electromyogram, or of the intestinal smooth muscle layers, etc., todetermine whether the electrical activity is abnormal, indicatingpossible disease.

Electrical stimulation of the gastrointestinal tract has been proposedto treat motility related disorders and other gastrointestinal diseases.The electrical stimulation has been proposed in a number of forms, suchas, e.g., pacing; electrical contractile stimulation or otherstimulation; e.g., to treat nausea. Electrical pacing of the intestinaltract is generally defined as periodic electrical stimulation thatcaptures and/or controls the frequency of the pacesetter potential orslow wave activity of the intestinal organ (including in a retrogradedirection). Electrical contractile stimulation generally refers tostimulation that directly causes or results in muscular contractionassociated with the intestinal tract.

In some disease states, dysrhythmias of the intestinal tract pacesetterpotentials may be present. Electrical pacing of pacesetter potentialshas been proposed to induce regular rhythms for the pacesetterpotentials with the intent of inducing regular or controlled intestinaltract contractions. Pacing has also been suggested to cause retrogradepropagation of pacesetter potentials. Also, electrical contractilestimulation of the intestinal tract has been proposed to induceperistalsis.

Many currently proposed intestinal tract electrical stimulationprocedures are relatively invasive and require accessing the intestinaltract through the abdomen, e.g., in an open or a laparoscopic procedure.The devices used typically require implanting permanent leads,electrodes and a pacemaker within the body. Therefore, it would bedesirable to provide a less invasive device for electrically stimulatingthe intestinal tract, particularly in combination with a system fortracking the device and delivering the treatment to an identifiedlocation.

SUMMARY OF THE INVENTION

The present invention provides a capsule having diagnostic and/ortreatment capabilities, and a system for tracking the capsule throughthe intestinal tract. One embodiment of a tracking system provides animproved system for determining the coordinates of a capsule inthree-dimensional space. According to this embodiment, an acousticsignal is transmitted between a capsule as it is passing through theintestinal tract, and a location external a patient's body. As such anacoustic transmitter or transmitters are located either at the capsuleor location external to the patient's body and the acoustic receiver(s)or sensor(s) are located at the other of either the capsule or locationexternal a patient's body. The velocity of an acoustic signal throughtissue is predictable (ultrasound transmits through tissue at about 1540meters per second). Using the amount of time the signal takes to travelto the receiver(s) and the signal velocity, the relative capsuledistance(s) to the location(s) external the patient's body isdetermined. Also, it should be noted that the transit time of theacoustic signal is linearly proportional to the distance traveled.

In one preferred embodiment, a capsule passing through the intestinaltract transmits an acoustic signal through the body to a plurality ofexternally located acoustic sensors. The relative capsule distances tothe sensors are determined using the amount of time the signal takes totravel to the receiver. Triangulation of the comparative distances willresult in a location of the capsule in space (for example, on aCartesian coordinate system).

According to a preferred embodiment, a reference signal is used toidentify the time of acoustic signal origination. In one variation,reference signal may be in the form of an RF reference signal deliveredfrom the capsule to an external sensor where the capsule emits theacoustic signal. In this variation, the RF reference signal is deliveredat predetermined time from the emission of the acoustic signal. The RFsignal, which travels at the speed of light, is received by the sensorsrelatively instantaneously. The RF signal is used by the sensor/receiverto determine when the acoustic signal was transmitted. Alternatively, inanother variation, an external, telemetrically delivered electromagneticcontrol signal may be used to trigger the emission of the acousticsignal from the capsule, thereby providing a time reference. Where theacoustic transmitter is at located externally of the patient, thereference signal, for example, may also be a trigger signal thattriggers emission of the acoustic signal from and external transducer.In various other embodiments, the reference signal may utilize othercommunication media to provide a reference signal. For example, aninfra-red link or a distributed resistive link could be used. Accordingto these alternative embodiments, signals may be transmitted either toor from the capsule.

Another embodiment provides a tracking system that tracks a capsule'slinear position along the intestinal tract length or a portion thereof.As the capsule moves through the tract, it senses diagnosticinformation. The tracking system correlates sensed diagnosticinformation with the capsule's corresponding linear position when theinformation is sensed. From the diagnostic information, a location alongthe length traveled is identified for treatment or therapeuticfunctions, which also include acting on the intestinal tract for atherapeutic purpose, e.g., to mark the location for surgicalintervention. A location along the length may also be identified forfurther diagnosis, including using subsequently passed capsules.

In a subsequent pass of a capsule, the capsule's linear position ismonitored until it reaches the position along the length identified by aprevious capsule. At that location, the subsequent capsule thenprovides, treatment, further diagnosis, or marking. Because theintestinal tract length is relatively constant, the tracking systemprovides a means for locating a portion of the intestinal tract that isrelatively independent of intestinal tract shifting or movement. Thus,the system also provides repeatable tracking independent of the locationof the sensors or pods on the patient. The system of this embodimentthus allows for subsequent passes of the capsule where the sensors orpods have been repositioned, for example in a later treatment cycle. Ina preferred embodiment, the sensors are provided with the ability toactively locate each other in a three dimensional coordinate system.This allows the sensors to re-calibrate to determine their relativelocation when they have moved due to respiration, or other patientmovement. Because the location of the capsule in a preferred embodimentof the tracking system depends on the relative location of the sensors,re-establishing the relative sensor location on a regular basiscompensates for sensor movement during a procedure using tracking.

Preferably, the position of a capsule along a length of the intestinaltract is determined by first identifying the capsule's 3-dimensionalposition over time, for example, on a Cartesian coordinate systemcreated by the pods. The tracking system includes a processor thatmonitors the signals from the pods and that uses incremental change inposition over time to convert the 3D capsule location information tolinear travel distance measurements. The linear travel distancemeasurements are then used to derive the capsule's position along thelength of the intestinal tract portion of interest. Preferably thetracking system uses acoustic transmission time from the capsule toexternal sensors to determine the capsules 3D coordinates as describedherein. An initial location of the capsule is preferably firstidentified, such as, when it reaches the pylorus. Such position may bedetermined by a number of means such as by determining capsule movementindicative that the capsule is moving from the stomach into the smallintestine, including, for example change in location, or acceleration.Alternatively a capsule's initial location may be determined, forexample by pressure, which changes when the capsule passes through thepylorus, or pH, which changes when the capsule enters the duodenum.

Another feature of the invention provides a system to compensate forvariations in capsule location determinations along the length of theintestinal tract that are due to intestinal smooth muscle contractionsand corresponding foreshortening of the intestinal tract. For example,pressure may be measured to determine the relativerelaxation/contraction of the tract and the correspondingforeshortening. The determination of capsule location may be a factor ofsuch pressure. Another feature of the invention provides a filter thatdetects and filters out capsule movement not corresponding to actualmovement along the length of the tract. For example, by observing theorientation and type of movement, movement that is not statisticallyrelated to movement along the intestinal length may be filtered out.

Another feature of the invention is a capsule having a plurality ofacoustic transducers to provide information concerning directionalorientation of the capsule.

Although the linear tracking system may not require sensing ofadditional parameters to determine location, the linear tracking is usedas a diagnostic tool when combined with other sensed information toprovide a diagnostic linear map of the intestinal tract or a portionthereof (such as the small intestine.) Further, the tracking system ispreferably combined with both diagnostic and treatment functions. Inuse, after a diagnostic capsule provides a diagnostic linear map of theintestinal tract, a treatment capsule is passed through intestinal tractportion. The treatment capsule that travels through the intestinal tractis monitored by the tracking system for its relative linear positionuntil it reaches a position along the intestinal tract length to betreated. The mechanism for providing the treatment is then actuated,typically by a telemetrically delivered control signal.

A number of capsules may be used as a combined diagnostic and treatmentsystem. For example, a first capsule obtains information on the capsuleposition along the intestinal length and corresponding diagnosticinformation (if desired, a diagnostic linear map of the tract). Anothercapsule may then be passed through the tract to provide treatment and/ordiagnosis at a desired location along the length of the tract. Once thelength of the tract has been mapped, any number of subsequent capsulesmay be passed through to further obtain diagnostic information or toprovide treatment. Using this technique a clear map of diagnosticinformation vs. length of intestine may be obtained. Additional capsulesmay be used at a later time using the same map for additional diagnosis,treatment or follow up. Also a combination of capsules may be swallowedin a spaced apart sequence where more than one capsule is in thedigestive system at one time.

A diagnostic capsule may sense a number of parameters such as, forexample, pH for assessing acidity levels in the intestinal tract,electrical activity, electrical impedance, optical parameters fordetection of specific reflected or transmitted light spectra, e.g.blood, objects or obstructions in the intestinal tract, pressure forintestinal tract manometric data acquisition and various diagnosticpurposes such as determining effectiveness of stimulation, blockages orconstrictions, etc., etc. An acoustic transducer, for example,piezoelectric crystals, may be used for performing diagnostic ultrasoundimaging of the intestinal tract etc. Also, a temperature transducer maybe used. Also, from the positional information over time, capsuletransit time, velocity, and acceleration may be calculated and used toidentify locations or segments of the intestine where there are motilitydisorders (such as segmental diseases).

A treatment capsule with the described tracking system subsequentlypassing through the identified portion to be treated will be signaled toprovide treatment. The treatment capsule may include but does notrequire any diagnostic sensors. The treatment capsules may perform oneor more of a number of treatment functions. Such treatment may takeseveral forms or combinations that may include, for example, deliveringan electrically stimulating signal, treating bleeding with ablation,clotting agents or coagulants, active or passive drug delivery or genetherapy treatment at specific portions of the tract, an inflatableelement for performing balloon plasty of the intestinal tract, forplacing a stent (e.g. for strictures), a self expanding stent deliverysystem, tissue biopsy or content sampling devices, or marking devices,(e.g. staining, marking or tattooing ink, such as india ink, methyleneblue or purified carbon powder; radiopaque dye; or magnetic devices)e.g., for locating a portion of the tract for surgery, etc.

One embodiment of the capsule system includes a sensor for detecting thepresence of blood. For example, an optical sensor or a chemical sensormay be provided that senses the presence of blood. The capsule is passedthrough the intestine and the location of the capsule along the lengthof the tract where the blood is sensed is identified. A treatmentcapsule having bipolar electrodes is then passed through the intestinaltract until it reaches the identified length of the tract where bleedingis occurring. An external power source is coupled to an RF coil withinthe capsule to deliver a current through the electrodes to ablate orcauterize the bleeding tissue. Alternatively, a site where bleeding ispresent may be treated using a subsequently passed capsule having aballoon tamponade, i.e. an inflatable member that uses compressionand/or a thrombogenic substance coated on the inflatable member to helpcause hemostasis.

Another embodiment of the capsule system comprises a diagnostic capsulethat includes a sensor (such as a pressure sensor) that identifies ablockage, stricture or narrowing of the intestine. The location of thecapsule along the length of the intestine is tracked. The sensedblockage is correlated to the capsules linear position along theintestinal tract. The tracking system tracks the linear position of atreatment capsule as it passes through the tract until it reaches thelocation of the blockage. An externally transmitted telemetric signalcauses a balloon plasty capsule to deploy an expandable member thatdilates the intestinal passage. In one variation, a variable sizeballoon may be used to determine the extent of a blockage. In thisvariation, for example, a balloon may be inflated at the suspectedblockage area. The balloon is gradually deflated until it passes throughthe blocked area. The diameter of the balloon when the balloon is ableto pass through the constricted site may, e.g., be used to determineextent of the blockage. The diameter of the balloon may be approximatedfrom the volume of inflation medium in the balloon. In another variationa balloon may be provided with an expandable support structure over theballoon such as a stent. The stent may be deployed within the intestinaltract when the balloon is expanded and thereby provide additional radialsupport of the intestinal wall.

Another embodiment of the capsule system provides a diagnostic capsulefor which position and corresponding diagnostic information are trackedalong the length of the intestinal tract. A location for surgicalintervention is identified based on the diagnostic information and asecond capsule is passed through the tract. When the second capsulereaches the linear position of the location for surgical intervention, atelemetric signal is delivered from an external device that triggers therelease of a marker within the tract at the desired location. Suchmarker may include, for example a radiopaque marker that may be locatedwith an x-ray system during a procedure, a fluorescing compound that isused to identify the location (e.g., fluorescein), or a dye that stainsthrough the wall of the intestine (e.g. staining, marking or tattooingink, such as india ink, methylene blue or purified carbon powder,radiopaque dye). The markers may assist a surgeon in a laparoscopic oropen procedure where such imaging systems are used during the procedureor where visualization is possible, e.g. of a stain.

In an alternative embodiment, a capsule may be used to mark a locationin the intestinal tract by affixing itself to the intestinal wall at anidentified location. Such capsule may include deployable anchormechanisms where an actuation mechanism causes the anchor to deploy. Forexample, an external telemetric command signal may trigger the releaseof such anchor. Such anchor may be provided in a number of formsincluding an expandable member, or other wall engaging mechanism. Thecapsule may also be provided with a light emission source such as alaser or an IR source, that emits light to enable location of thecapsule, preferably when the capsule is affixed to the intestinal wall.

Another embodiment of the treatment capsule system is an ingestiblecapsule that will electrically stimulate a predetermined portion of theintestinal tract. Electrical stimulation is generally defined herein tomean any application of an electrical signal or of an electromagneticfield to tissue of the intestinal tract for a therapeutic purpose or toobtain diagnostic information. According to this embodiment, electricalsignals are delivered to intestinal tract tissue by at least oneelectrode, preferably a bipolar electrode pair, or one or more selectedelectrode pairs coupled to the capsule that electrically stimulates theintestinal tract as the capsule passes through it.

The electrodes deliver a signal that is designed to cause desiredtherapeutic effect, for example, a smooth muscle response, i.e.,stimulation or inhibition of contraction or peristaltic motion. Theelectrodes may deliver the electrical stimulation to the smooth muscleby contacting, for example, the tissue that forms the intestinal liningor the mucosal tissue of the intestinal tract.

In one preferred treatment method, the electrical stimulation signalentrains a slow wave signal of a portion of the intestinal tract smoothmuscle that is clinically absent, weak, of an undesirable frequency,sporadic or otherwise not optimal. Also, the capsule may transmit otherelectric stimuli. In one embodiment the electrical stimulus is designedto trigger the spike burst electrical activity of the smooth muscleassociated with smooth muscle contractions. The stimulating signals mayalso be designed to inhibit the inherent smooth muscle pacingpotentials, to reduce smooth muscle contractions. The signals may alsobe designed to disrupt the natural waveform and effectively alter theexisting or inherent pacing.

The stimulation electrodes provide stimulation either by way of apreprogrammed generator or one that is programmed while the capsule isin the intestine, e.g., based on sensed parameters or response tostimulation. In one embodiment, the capsule acts as a slave to anexternal device providing master stimulation signals that are receivedby the capsule and delivered to the tissue.

The stimulation capsule of the present invention may include a pluralityof electrodes that may be utilized for forward or backward electricalstimulation, e.g., where the order in which a series of electrode pairsare activated can cause peristalsis to move in a directional manner. Aplurality of electrode or bipolar electrode pairs may be provided. Suchelectrodes, electrode pairs or combination of electrodes or electrodepairs may be selected for delivering stimulation pulses, (eitherpreprogrammed or programmed while the electrodes are deployed in theintestine) to optimize various parameters, e.g. impedance, currentdensity, optimal tissue contact, etc.

The capsule is swallowed or alternatively delivered endoscopically to apredetermined portion of the intestinal tract. The capsule is sized andhas a conformity such that it can then readily pass through theintestinal tract. For example, the capsule may pass from the stomach tothe small intestine to the colon and exit from the intestinal tractthrough a bowel movement, permitting its recovery if desired. Also, thecapsule may, in general, move with the food material as it passesthrough the intestinal tract.

The capsule is preferably provided with RF or other signal transmissioncapabilities, e.g., light. The signal transmission may be used in anumber of manners. As described above, the system may have RF signaltransmission capabilities that enable determination of a location of thecapsule by providing a reference for the time of the acoustic signalinitiation.

The signal transmission capabilities may also be used for telemetriccommunication between the capsule and an external device, e.g., tocommunicate data to the external device or to receive additional capsuleprogramming information, command signals, or stimulation signals fromthe external device.

The capsule may be used to sense electrical parameters. For example thecapsule electrodes can be used to sense native pacesetter potential(slow wave activity) as well as spike burst activity which correspondsto muscular contractions. The electrodes may also be used to determinetissue impedance. By recording the electrically sensed signals andcombining that information with tracking information a comprehensiveknowledge of the electrical behavior of the intestinal tract can begained. Information such as absence of slow wave activity, slow wavefrequency, presence of spike burst activity, number of spike burstevents per slow wave, and spike burst frequency can assist the clinicianin detection and pinpoint location of various disorders such asintestinal neuropathy, tachyarrhythmia, ileus, etc. Preferably theelectrical characteristics are correlated to the capsule's movementalong the length of the tract to provide a diagnostic linear map of theintestinal tract.

A number of capsules may be passed through in series so that thecapsules follow each other in short spaced time intervals. A firstcapsule provides diagnostic information correlated to the capsule'sposition along the length of the intestine. A subsequent capsule mayprovide electrical stimulation based on the sensed conditions. A numberof capsules may be passed through, each time obtaining diagnosticinformation or providing treatment according to the linear map.

The electrical stimulation capsule may be provided with one or moresensors for sensing various conditions in the intestinal tract. Also,the information obtained by the sensors may by communicated viatelemetry to a control or locating device that evaluates the sensedinformation and sends a control signal to the capsule in response,instructing the capsule to perform a particular function or may providesuch stimulation signals to the capsule to be delivered through theelectrodes on the capsule. The capsule may combine the electricalstimulation feature with other therapeutic or diagnostic capsulefunctions such as, for example, drug delivery, biopsy or other materialsample recovery, etc. Finally, the sensed parameter may be used toascertain whether or not the stimulated portion is contracting inresponse to electrical stimuli received from the capsule. For example,the pressure or change in pressure within the tract at a particularlocation may be indicative of a contractive response to electricalstimulation.

As an alternative to relying on the tracking system described herein, anelectrical stimulation capsule may respond to the sensed information byperforming a function, such as, for example, by initiating, altering orceasing delivery of stimulation signals upon sensing of electricalactivity, pressure or pH conditions that identify the location of thecapsule or condition of the intestinal tract at the location.

In a variation, the inventive capsule includes an encasing at least aportion of which is dissolvable in fluids in the intestinal tract. Theencasing may selectively dissolve depending on the pH of the tract. Forexample, the encasing may dissolve in the small intestine where the pHis substantially neutral in comparison to the acidic stomach conditions.Dissolving the encasing may release a component contained within thecapsule for example, so that encased electrodes are exposed or deployedat a desired location.

Another feature of the invention is a capsule having the capability offunctioning regardless of the directional orientation in the intestinaltract.

In a preferred embodiment, the capsule and method described above areused in stimulating the small intestine. One variation of thisembodiment provides for small intestine pacing.

Additional features of the invention will appear from the followingdescription in which the preferred embodiments are set forth in detailin conjunction with the accompanying drawings.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the tracking system of the present inventionpositioned on a user.

FIG. 2 is a side partial cross-sectional view of a pod of the trackingsystem of FIG. 1.

FIGS. 3A and 3B are partial cross-sectional views of a first embodimentof a capsule of the present invention with tracking capabilities, usedwith the tracking system of the present invention.

FIG. 4 illustrates the electronic circuitry of the capsule illustratedin FIG. 1.

FIG. 5 illustrates a schematic of the electronics of the recorder of thetracking system of the present invention.

FIG. 6 illustrates the pods such as the one illustrated in FIG. 2 set upin an x, y, z Cartesian coordinate system.

FIG. 7 illustrates the location of a capsule on the x, y, z Cartesiancoordinate system of FIG. 6.

FIGS. 8A-G illustrate a timing diagram of signal emission and receptionof an exemplary tracking system of the present invention.

FIG. 8A illustrates the emission of the RF reference signal.

FIG. 8B illustrates the emission of an ultrasound signal from thecapsule.

FIG. 8C illustrates the timing of the reception of the RF referencesignal by the Pods.

FIG. 8D illustrates the timing of the reception of the ultrasonic signalat the first Pod.

FIG. 8E illustrates the timing of the reception of the ultrasonic signalat the second Pod.

FIG. 8F illustrates the timing of the reception of the ultrasonic signalat the third Pod.

FIG. 8G illustrates the timing of the reception of the ultrasonic signalat the fourth Pod.

FIG. 9 illustrates a partial cross-sectional view of a second embodimentof a capsule of the present invention.

FIG. 10 illustrates a partial cross-sectional view of a third embodimentof a capsule of the present invention.

FIG. 11A illustrates an example of the length of a gastrointestinalsystem.

FIG. 11B illustrates an example of a map of pH as sensed in relation tothe linear position of a capsule along the length of the tract of FIG.11A.

FIG. 11C illustrates an example of a map of pressure as sensed inrelation to the linear position of a capsule along the length of thetract of FIG. 11A.

FIG. 11D illustrates an example of a map of electrical activity assensed in relation to the linear position of a capsule along the lengthof the tract of FIG. 11A.

FIG. 12 illustrates a partial cross-sectional view of a fourthembodiment of a capsule of the present invention.

FIG. 13 illustrates the electronic circuitry for the capsule of FIG. 12,including ablation electronics.

FIG. 14 illustrates the electronic circuitry for an external powersource for the ablation function of the capsule of FIG. 12.

FIG. 15 is a partial cross-sectional view of a fifth embodiment of acapsule of the present invention having a dissolvable encasingcontaining a deployable stimulation electrode.

FIG. 16 is a side elevational view of the capsule shown in FIG. 15 withthe encasing dissolved and the deployable stimulation electrodedeployed.

FIGS. 17A and 17B are graphs showing the programmable pacing parametersof the capsule shown in FIGS. 15 and 16.

FIG. 18 is a side elevational view of a sixth embodiment of the capsuleof the present invention.

FIG. 19 is a cut away view of a seventh embodiment of a capsule of thepresent invention and showing stimulation electrodes wrapped about thecapsule and encapsulated in a dissolvable encasing that is partially cutaway.

FIG. 20 is a partial cross sectional view of the embodiment of FIG. 19with the electrodes deployed.

FIG. 21 is a partial cross sectional view of an eighth embodiment of acapsule of the present invention with pressure sensing capabilities.

FIG. 22 is an enlarged cross sectional view of a portion of the capsuleshown in FIG. 21.

FIG. 23 illustrates alternative electronic circuitry that may be usedwith the stimulation capsule.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIG. 1, there is illustrated a tracking system 160 of thepresent invention positioned on a patient. The tracking system 160comprises an external recorder 105; four pods 101, 102, 103 and 104respectively, containing both acoustic and EM emitter/receivers; and acapsule 110 that is swallowable or otherwise positionable to move withinan intestinal tract. The recorder 105 is secured to the external abdomenof the patient. The pods 101, 102, 103 and 104 are adhered to the skinof the patient and have an acoustic transmitting/coupling material,e.g., a gel layer, interfacing between the skin of the patient and thepods 101, 102, 103, 104.

As illustrated in FIG. 2, the pod 101 comprises an outer plastic casing106 enclosing an acoustic transducer 107 a and an RF coil 108 a. Thecasing 106 has an interfacing wall 106 a for interfacing with the skinof a patient. An adhesive layer 109 is formed on a portion of theinterfacing wall 106 a, for adhering the pod 101 to the patient's skinwhile a remaining portion of the interfacing wall 106 a is exposed tothe patient's skin. The acoustic transducer 107 a is attached to thewall 106 a within the casing 106 adjacent the exposed portion of thewall 106 a in a manner that allows the acoustic or ultrasonic energy totransmit through the interfacing wall 106 a. On the opposite side of theacoustic transducer 107 a, an acoustic backing material 107 m isprovided that absorbs the acoustic energy transmitted in the directiontowards the backing material 107 m. Typically a gel or otheracoustically transmitting/coupling material is placed on the outside ofthe exposed portion of the interfacing wall 106 a. The output of theacoustic transducer 107 a is coupled to wires 100 a that are coupled tothe recorder 105 through the wire conduit 100 extending out of thecasing 106. The RF coil 108 a is coupled through wires 100 b alsoextending through wire conduit 100 to recorder 105. Pods 102, 103, and104 are similarly constructed.

As illustrated in FIGS. 3A and 3B, a first embodiment of a capsule 110comprises a liquid impermeable and airtight capsule body 111. Ingeneral, the capsule of the present invention is sized so that it iscapable of being ingested for passage through the intestinal tract. Foradult human use, a preferred embodiment of the capsule is to be sized sothat it has a length ranging from about 1.5 to 2.5 cm and having adiameter of about 8 mm or less. For children and larger and smalleranimals, the capsule can be appropriately sized. The capsule body 111contains and protects the enclosed circuitry from body fluids whilepassing through the intestinal tract. At least a portion of the capsulebody 111 is constructed of an ultrasound transmitting material that iscompatible for use in the human body such as, for example, a medicalgrade plastic, e.g., polyethylene. A radiopaque marker 111 a is embeddedin the plastic casing so that in the event it is necessary to locate thedevice via an external imaging source, its location may be identified. Adissolvable encasing (not shown) may surround the capsule body 111. Theencasing may be formed of a suitable dissolvable material such as, forexample, a soluble gelatin or enteric coating that is dissolvable in thebody fluids contained in the stomach or intestinal tract. Such materialsmay be selectively dissolved based on the pH condition so that theencasing dissolves after the capsule 110 has passed through the highlyacidic stomach and into the more neutral small intestine. The capsulebody 111 includes a generally hemispherical back end 131 and a generallyhemispherical front end 132. The back end 131 includes an inner endsurface 131 a. The front end 132 includes an inner end surface 132 a.The overall conformation of the ingestible capsule 110 is cylindrical inshape forming a substantially smooth outer capsule surface.

The capsule 110 includes an RF coil 135 for transmitting and receivingRF signals, and an acoustic transducers 136 a, 136 b, and 136 c locatedwithin the capsule body 111. The acoustic transducers 136 a and 136 bare located against the inner end surfaces 132 a and 131 a respectivelywith an acoustic transmitting/coupling material filling any gap betweenthe transducers 136 a and 136 b and the end surfaces 132 a, 131 a in amanner so that the transducers can transmit acoustic, preferablyultrasonic waves through the capsule body 111 to the surrounding tissueor material. Acoustic transducer 136 c is cylindrical in shape,extending around an inner circumference of the capsule. An acoustictransmitting/coupling material similarly fills any gap between theacoustic transducer 136 c and the inner wall of the capsule body 111.The acoustic transducers 136 a-c are arranged in combination to transmitacoustic signals relatively omni-directionally.

The transducer 136 a comprises a piezoelectric crystal 137 locatedbetween electrode plates 138 that when energized cause the crystal tooscillate at an ultrasonic frequency (preferably between 100 kHz and 5MHz). An acoustic backing material 139, such as, oxide particles in aflexible polymer, e.g., an epoxy matrix tungsten powder, is placed onthe back of the transducer 136 a to absorb any acoustic transmissions ina direction opposite to the end surface 132 a. The acoustic transducers136 b and 136 c are constructed in a similar manner to transducer 136 aand of similar materials. Other configurations of an acoustic transduceror transducers may be used to provide relatively omni directionalacoustic signal transmission. The RF coil 135 and the acoustictransducers 136 a, 136 b and 136 c are electrically coupled to theelectronics 113 which is powered by battery 114.

An elongate member 115 is affixed to the back end 131 of the capsulebody 111. First and second bipolar electrodes 116, 117 are located onthe elongate member 115, the second bipolar electrode 117 beingelectrically opposite of the first electrode 116. The elongate member115 is preferably formed of an elastically behaving material such as aNi—Ti alloy.

The capsule body 111 also includes a pH sensor 133 on the capsule body111. The pH sensor 133 is formed with dissimilar metals such as, e.g.,silver chloride and antimony that sense differences in pH and convertthe sensed result into a calibrated electrical signal. The pH sensor iscoupled to the electronics 113 by electrical conductors.

Referring now to FIG. 4, the electronic circuitry 113 of the capsule 110is illustrated. The electronic circuitry 113 is a chip that includes anumber of optional connectors, and, as such, may be used in a number ofdifferent diagnostic or therapeutic capsule configurations. Theelectronic circuitry 113 of the capsule 110 comprises, a microprocessoror controller 122 for controlling the operations of the electroniccircuitry, an internal clock 121, and battery device 114 such as a pairof lithium iodine batteries, for powering the various components of thecircuit 113. As such, the controller 122 and battery device 114 arecoupled to each of the major components of the circuit as would be knownto one of ordinary skill in the art.

The controller 122 is coupled to ROM 123, which contains the programinstructions for the controller 122 and any other permanently storedinformation that allows the microprocessor/controller 122 to operate.The controller 122 addresses memory in a location in ROM 123 throughaddress bus 123 a and the ROM 123 provides the stored programinstruction to the controller 122 via data bus 123 b.

The electrode plates 138 of the acoustic transducer 136 a are poweredthrough oscillator 137 a controlled by the controller 122 to produce adesired acoustic wave output. Similarly, electrode plates of acoustictransducers 136 b and 136 c are powered through oscillators 137 b and137 c, respectively, controlled by the controller 122. The controller122 controls the RF coil 135 that acts either to deliver an RF trackingsignal or as a telemetry device for communicating data to the recorder105. The RF coil 135 delivers signals to or receives signals from the RFcoils 108 a-d (FIG. 5) in the pods 101, 102, 103, and 104. For trackingpurposes, controller 122 will respectively, at fixed time intervals,order the transmission of an RF signal and an acoustic signal using theRF coil 135 and at least one of acoustic transducers 136 a-136 c. Thecontroller's commands will incorporate a preset time interval betweenthe RF signal transmission and acoustic signal initiation. Such timeinterval (which could be zero) will be factored in at the recorder 105to determine acoustic wave transmission time. In the preferredembodiment, the capsule's acoustic transducers 136 a-136 c transmit theacoustic signals immediately, or a defined time after the RF referencesignal. The acoustic transducer 136 a will emit a first signal apredetermined time after the RF signal, the second and third acoustictransducers 136 b and 136 c will emit second and third signalsrespectively at predetermined times after the RF signal and sufficientlyspaced in time from the other signals so that the acoustic signals maybe differentiated. Alternatively, the second and third acoustic signalmay be referenced from second and third differentiated RF signals.

When the RF coil 135 is receiving an external telemetry signal, thebuffered oscillator 119 is disabled. Telemetry signals received on RFcoil 135 are detected in a detector circuit 119 a and communicated tomicroprocessor 122. The detector circuit 119 a is preferably selectedbased on the modulation used for the telemetry signals.

One or more sensors, e.g., 127 a (pressure), 127 b (pH), 127 c(optical), 127 d (temperature), and 116, 117 (electrodes) may be coupledto controller 122 through A/D converters (with amplifiers) 126 a, 126 b,126 c, 126 d, 126 e which convert a representative analog electricalsignal into a digital signal. Suitable sensors of these types aregenerally known in the art and may be located within, on, or external tothe capsule body 111. The electrodes 116, 117 used to deliver thestimulation are also used to sense electrical activity or impedance asdescribed in further detail herein.

The controller 122 is coupled to RAM 120 via an address bus 120 a foraddressing a location in RAM 120 and a bi-directional data bus 120 b fordelivering information to and from RAM 120. The RAM 120 includes eventmemory 124 that temporarily stores data recorded by sensors 127 a-127 dand electrodes 116, 117. RAM 120 also includes a programmable memory 125which may be programmed, for example, via telemetry while the capsule110 is within the intestinal tract, to provide treatment protocols. Thedata stored in the event memory 124 may be sent to external coils 108a-d (FIG. 5) intermittently as data bursts via telemetry through the RFcoil 135, as opposed to continuously in order to save battery power. Thedata stored in the programmable memory 125 may include specificationsfor the electrical stimulation operating modes (e.g. waveform, type ofstimulation: for pacing, inducing contraction or other type) and variousprocedure parameters (e.g., when to deliver a drug or electricalstimulation). Such programming may be done in response to sensedinformation or it may be done automatically by an external controller oras desired by a treating physician, etc.

Controller 122 is coupled to a buffered oscillator 119 that provides anRF signal to be emitted from the RF coil 135. The RF signal ispreferably at about 100 kHz to about 5 MHz so that the signal isefficiently transmitted through tissue. The controller 122 controls theoscillator 119 and provides data for example, various sensed data suchas pressure, pH, impedance, electrical activity, etc., to be modulatedwith the RF signal to be delivered through RF coil 135. The controller122 may also be coupled through stimulation driver 118 and couplingcapacitors 116 a, 117 a to bipolar stimulating electrodes 116, 117,respectively. Electrical stimulation may be provided in a manner similarto that described herein with reference to the stimulating electrodes 16a-c, 17 a-b, 56, 57, 66, 67, 86, and 87 of FIGS. 15-22. The stimulationmodes and parameters can be preprogrammed or set by an external devicethat telemetrically communicates the parameters.

The battery 114 has its output supplied to a DC-to-DC converter 130 toprovide a higher voltage, which is utilized for electrical stimulationpulses. The DC-to-DC converter 130 is conventional and provides anoutput voltage of 15 to 20 volts. Further the circuit 113 may includeone or more drivers 128 a, 128 b, 128 c, 128 d that drive variousdevices, for example, diagnostic or therapeutic electromechanicaldevices, such as controlling valves, solenoids, etc, for, e.g., drugdelivery, biopsy, content sampling, or a marker release, etc. Thecontroller 122 provides a signal to a driver 128 a-128 d based on apreset program in ROM 123, on sensed parameters stored in RAM 120,and/or on a telemetrically received signal from the recorder 105 or RFcoils 108 a-d in the pods, 101-104. The circuit may also include astepping driver 129 coupled to a stepper motor for example for rotatingan imaging device (e.g., diagnostic ultrasonic device) or actuating abiopsy device, etc.

Referring now to FIG. 5, a schematic of the electronic circuitry 140 ofthe recorder 105 of the present invention is illustrated. The electroniccircuitry 140 of the recorder 105 comprises: a microprocessor orcontroller 142 for controlling the operations of the electroniccircuitry, an internal clock 141, and power source such as a battery 147for powering the various components of the circuit 140. The controller142 and battery device 147 are coupled to each of the major componentsof the circuit in a manner known to one of ordinary skill in the art.

The electronic circuitry 140 is coupled to the pods 101, 102, 103 and104, which respectively include RF coil sensors 108 a-d and acoustictransducers 107 a-d that send and receive signals to and from thecapsule 110. The details of the coupling of the transducer 107 a and 108a are illustrated in FIG. 5. The transducers 107 b-d and coils 108 b-dare coupled in a similar manner not shown. The output of the RF coil 108a is coupled through a demodulator 155 to the controller 142. Thedemodulator 155 demodulates the information carried by the RF signalreceived by the RF coil 108 a. Such information may include, forexample, telemetrically delivered sensed data. Also, the RF coil 108 amay emit an RF reference signal. The controller 142 controls the outputof the RF coil 108 a, which communicates with the capsule 110. Thecontroller 142 is coupled to an oscillator 156 that provides a carriersignal, preferably having a characteristic frequency in the range of 100kHz to 5 MHz so that it may be efficiently transmitted through tissue tothe capsule. The controller 142 provides data to be modulated with theRF signal, for example, commands to the capsule 110 to providetreatment, treatment parameters, etc. The controller 142 controls theoutput of acoustic transducer 107 a through oscillator 157, whichprovides the oscillating frequency to the transducer when the pod ispinging another pod, i.e., when the pods are sending signals tocalibrate the pods and identify their locations on the coordinatesystem. The controller 142 also receives the representative acousticsignal from the transducer 107 a through automatic gain control device158 which brings the voltage or current levels within a predefinedrange, and through filter 159.

The controller 142 is further coupled to ROM 143, which contains theprogram instructions for the controller 142 and any other permanentlystored information that allows the microprocessor/controller 142 tooperate. The controller 142 addresses memory in ROM 143 via address bus143 a and the ROM 143 provides the stored program instruction to thecontroller 142 via data bus 143 b.

The controller 142 is coupled to RAM 144 via address bus 144 a andbi-directional data bus 144 b. The RAM 144 comprises event memory 145that temporarily stores data sent via telemetry from the capsule 110 tothe RF coils 108 a-d in the pods 101-104 until the data is downloadedonto a computer using external data port 150. For tracking purposes, theRAM 144 is also used to store the data concerning lag times between theRF signal and acoustic signals received by transducers 107 a-d, and RFcoils 108 a-d in the pods 101-104. The RAM 144 also comprises aprogrammable memory 146, which is used to specify operation modes (e.g.waveform, type of stimulation: for pacing, inducing contraction or othertype) and various procedure parameters that may be transmitted to thecapsule 110 through RF coils 108 a-d via telemetry. The recorder 105also includes a display 151 to show recorded data, sensed parameters,treatment parameters, and status of device (e.g., capsule position,battery charge status, etc.). The recorder 105 also includes a datainput device 152 such as a keyboard, pad or input screen for inputtingnew parameters, programming the capsule, changing the treatment scheme,viewing various data or turning the device on or off. The input iscoupled through a buffer 154 to the controller 142. The controller 142is coupled to a speaker 153 for providing audible information such as analert.

In FIGS. 6 and 7, the pods 101, 102, 103, and 104 are set up in anCartesian (x,y,z) coordinate system. The origin of the coordinate systemis defined as the location of pod 101. The y-axis is defined as the linethat passes through pod 101 and pod 102. The x-y plane is defined as theplane that intersects pods 101, 102 and 103. The z-axis is perpendicularto the x-y plane. Pod 104 is located off of the x-y plane. Thus, thecoordinates of the pods in this defined coordinate system are:

Pod 101: (0, 0, 0)

Pod 102: (0, y₂, 0)

Pod 103: (x₃, y₃, 0)

Pod 104: (x₄, y₄, z₄)

where the pod coordinates y₂, x₃, y₃, x₄, y₄, and z₄ are initiallyunknown.

Once the pods are placed as illustrated in FIG. 1, the coordinates ofthe pods are initially determined in the following manner. Asillustrated in FIG. 6, the distances d₁₂, d₁₃, d₁₄, d₂₃, d₂₄, and d₃₄represent the distances between pods 101 and 102, 101 and 103, 101 and104, 102 and 103, 102 and 104, and 103 and 104, respectively. The pods,which can both emit and receive electromagnetic and acoustic (includingultrasound) signals, will sense time-lags between the RF and acousticsignals sent between the pods along the distances d₁₂, d₁₃, d₁₄, d₂₃,d₂₄, and d₃₄, i.e., the pods will ping each other. The pods communicatewith a processor located in the recorder that calculates the distanceand determines the coordinates. The time-lags are multiplied by thevelocity of sound to calculate the distances (d₁₂, d₁₃, d₁₄, d₂₃, d₂₄,and d₃₄) between the pods.

Under Pythagoras' Theorem the following six equations relate thecoordinates of the pods and the distances between them:(x ₂ −x ₁)²+(y ₂ −y ₁)²+(z ₂ −z ₁)² =d ₁₂ ²  (1)(x ₃ −x ₁)²+(y ₃ −y ₁)²+(z ₃ −z ₁)² =d ₁₃ ²  (2)(x ₄ −x ₁)²+(y ₄ −y ₁)²+(z ₄ −z ₁)² =d ₁₄ ²  (3)(x ₃ −x ₂)²+(y ₃ −y ₂)²+(z ₃ −z ₂)² =d ₂₃ ²  (4)(x ₄ −x ₂)²+(y ₄ −y ₂)²+(z ₄ −z ₂)² =d ₂₄ ²  (5)(x ₄ −x ₃)²+(y ₄ −y ₃)²+(z ₄ −z ₃)² =d ₃₄ ²  (6)

The pod coordinates x₁, y₁, z₁, x₂, z₂, and z₃ are defined as having thevalue of 0. Thus, plugging in the known pod coordinates, the equationscan be rewritten as:y ₁ ² =d ₁₂ ²  (1′)x ₃ ² +y ₃ ² =d ₁₃ ¹²  (2′)x ₄ ² +y ₄ ² +z ₄ ² =d ₁₄ ²  (3′)x ₃ ²+(y ₃ −y ₂)² =d ₂₃ ²  (4′)x ₄ ²+(y ₄ −y ₂)² +z ₄ ² =d ₃₄ ²  (5′)(x ₄ −x ₃)²+(y ₄ −y ₃)² +z ₄ ² =d ₃₄ ²  (6′)

With these six equations, and the determined distances, d₁₂, d₁₃, d₁₄,d₂₃, d₂₄, and d₃₄, the six pod coordinates, y₂, x₃, y₃, x₄, y₄, and z₄may be solved. Single solutions for all the coordinates may be obtainedby setting the following position restrictions: y₂>0; x₃>0; and z₄>0. Inother words, pod 101 should be placed on the right side of the user, pod102 on the left side, pod 103 on the lower abdomen, and pod 104 on theupper abdomen as illustrated in FIG. 1.

The determination of the solutions for the six pod coordinates y₂, x₃,y₃, x₄, y₄, and z₄ are described below:

Equation (1′) gives:y ₂ =d ₁₂  (1″)Plugging (1″) into (4′) and subtracting (4′) from (2′) gives:y ₃=(d ₁₂ ² +d ₁₃ ² −d ₂₃ ²)/(2d ₁₂)  (2″)Plugging (2″) back into (2′) gives:x ₃=(d ₁₃ ² −y ₃ ²)^(0.5)  (3″)where y₃ has been solved above.Plugging (1′) into (5′) and then subtracting (5′) from (3′) gives:y ₄=(d ₁₂ ² +d ₁₄ ² −d ₂₄ ²)/(2d ₁₂)  (4″)Subtracting (6′) from (3′) gives:x ₄=(d ₁₄ ² −d ₃₄ ² +x ₃ ² +y ₃ ²−2y ₃ y ₄)/(2x ₃)  (5″)where x₃, y₃ and y₄ have been solved above.Plugging (4″) and (5″) into (3′) gives:z ₄=(d ₁₄ ² −x ₄ ² −y ₄ ²)^(0.5)  (6″)where x₄ and y₄ have been solved above.

The pod coordinates are determined whenever the pods are repositioned.The pod coordinates may also be re-established at regular intervals toaccount for movement and thus relative change in pod position.

As illustrated in FIGS. 7 and 8A-G, using the coordinates of the pods,the location of the capsule in space may be determined as follows. Therange-finding capability of the pods measure the distances between thecapsule 110 and each pod. As illustrated in FIGS. 8A-B, the capsule 110emits an RF signal 205 and a synchronized ultrasonic signal 206 that isemitted a predetermined time interval after the RF signal 205 isemitted. In the preferred embodiment the ultrasound signal 206 isemitted immediately following the RF signal 205. In this drawing, forillustrative purposes the signal emitted from transducer 136 a isillustrated. Second and third acoustic signals emitted from the secondand third transducers 136 b and 136 c would be similar to the signalemitted from transducer 136 a except that they preferably emitted afterthe first signal 206 and at predetermined time intervals from the RFsignal 205. The signals from the additional acoustic transducers 136 band 136 c may also alternatively have different waveforms as that of thefirst signal 206. FIG. 8C illustrates the timing of when the RF signal205 is received at the pods. FIGS. 8D-G illustrate the timing of whenthe ultrasound signal 206 is respectively received at pods 101, 102,103, and 104. Because the RF signal 205 travels at the speed of light,it is received by the pods 101, 102, 103 and 104 at a relativelynegligible time delay in comparison to the ultrasonic signal whichtravels generally at about 1540 meters per second in human tissue. Thedistances c.sub.1, c.sub.2, c.sub.3, and c.sub.4 represent the distancesbetween the capsule and pods 101, 102, 103, and 104, respectively. Thepods 101, 102, 103 and 104 receive the ultrasound signal 206 transmittedfrom the capsule 110 at varying times depending on the distancesc.sub.1, c.sub.2, c.sub.3, and c.sub.4 respectively. Such time lags maybe represented as illustrated, for example, in FIG. 8 as t.sub.1,t.sub.2, t.sub.3, and t.sub.4 corresponding to distances c.sub.1,c.sub.2, c.sub.3, and c.sub.4, respectively. The time-lags will then bemultiplied by the velocity of sound to calculate the distances (c.sub.1,c.sub.2, c.sub.3, and c.sub.4) between the capsule 110 and each pod.

Using Pythagoras' Theorem the following equations relate the coordinatesof the capsule (x_(n), y_(n), z_(n)) and pods, and the distance betweenthem:(x _(n) −x ₁)²+(y _(n) −y ₁)²+(z _(n) −z ₁)² =c ₁ ²  (7)(x _(n) −x ₂)²+(y _(n) −y ₂)²+(z _(n) −z ₂)² =c ₂ ²  (8)(x _(n) −x ₃)²+(y _(n) −y ₃)²+(z _(n) −z ₃)² =c ₃ ²  (9)(x _(n) −x ₄)²+(y _(n) −y ₄)²+(z _(n) −z ₄)² =c ₄ ²  (10)These four equations may be solved to obtain a single solution for thethree coordinates of the capsule, x_(n), y_(n), and z _(n).

According to one embodiment, a three-dimensional or four-dimensional mapof the capsule's trip through the intestinal system can be generated bymeasuring the capsule's coordinates at fixed time intervals.

Alternatively, linear travel distance measurements can be made by usingPythagoras' Theorem. Incremental linear distances can be calculated andthen summed to obtain a total linear travel distance (L):L=Σ _(o) ^(m)[(x _(n+1) −x _(n))²+(y _(n+1) −y _(n))²+(z _(n+1) −z_(n))²]^(1/2),where m is equal to the number of incremental distances and where(x_(n), y_(n), z_(n)) and (x_(n+1), y_(n+1), z_(n+1)) are consecutivecapsule coordinate measurements used to measure incremental lineardistances traveled. In this manner a linear map of the capsule'sposition along the intestinal tract may be obtained. Such a map showsthe position of the capsule along the tract independent of actual 3Dspatial orientation. Thus, errors based on intestinal shifting,peristaltic motion, patient positioning, and change in pod location arereduced without requiring additional sensed information. Retrogradeperistaltic motion can occur in the small intestine. An algorithm may beused to cancel out any backtracking travel measurements when calculatingthe linear distance traveled by the capsule. As described below using anadditional acoustic transducer, (e.g., located on the opposite end ofthe capsule) and obtaining the same positional information may provideinformation on capsule orientation and direction of capsule movement.Preferably, the additional transducer will deliver a signal at timeintervals between the acoustic signals of the first transducer. Thesignals from the additional transducer may have a different waveform todifferentiate the signal from signals corresponding to the firsttransducer. The orientation information may provide additionalinformation that is used to cancel out retrograde capsule movement.

Referring to FIGS. 11A-D, an example of a linear map of an intestinaltract and corresponding maps of sensed information are illustrated. FIG.11A illustrates an example of a linear map of a gastrointestinal tract.FIG. 11B illustrates an example of a map of pH sensed by a capsule inrelation to its linear position along the length of the tract of FIG.11A. FIG. 11C illustrates an example of a map of pressure sensed by acapsule in relation to its linear position along the length of the tractof FIG. 11A. FIG. 11D illustrates an example of a map of electricalactivity sensed by a capsule in relation to its linear position alongthe length of the tract of FIG. 11A. These maps may be plotted fromsensed information on a display screen in the illustrated format or asotherwise may be desirable by a user.

The parameters shown in the maps in FIGS. 11B-D may be determined by acapsule having sensing capabilities. As the capsule passes through theintestinal tract and its location along the length is determined, otherparameters relating to the condition of the intestinal tract may besensed periodically or continuously. The sensed conditions may be sentvia telemetry to one or more pod receivers. This may occur independentlyfrom the time of the RF reference signal transmission and the acousticsignal transmission so that the telemetry signal is independent of thecoordinate determining RF reference signal. The sensed information ismapped along the length of the intestine by the tracking system asdescribed above. A linear map of sensed information is overlaid on thelinear map of the intestine so that unusual parameter values, or areasto be treated may be determined. Upon a second pass of a capsule, thearea or portion of the tract to be treated may be located along thelength of the linear map created from the first capsule pass. The secondcapsule uses a similar method to determine its position along the lengthof the tract and its linear travel position is compared to the lineartravel position of the first capsule. Thus, when the capsule hastraveled the appropriate position along the tract, the segment of thetract may then be treated. Treatment may be triggered by a telemetricsignal sent to the capsule when the recorder and external controllerhave calculated the appropriate linear position.

Referring now to FIG. 9, there is illustrated a second embodiment of atreatment capsule of the present invention. Capsule 170 comprises acapsule body 171 including an electronic circuit 113 and battery 174coupled to the electronic circuit 113. An RF coil 175 and acoustictransducers 176 a-c operate in a similar manner as RF coil 135 andtransducers 136 a-c described herein. The capsule further comprises acompressed gas source 165 and an inflatable balloon 167 externally fixedto the capsule body 171. The gas source 165 is in fluid communicationwith a valve 166 that opens into a chamber 168 in the balloon 167. Thechamber 168 of the balloon 167 further is in fluid communication with avalve 169 that opens to a gas exit port 172 that is in fluidcommunication with the intestinal tract. The valves are coupled throughdrivers 128 a, 128 b in electronic circuit 113. The operation of thevalves 166, 169 is controlled by the controller 122 in the electroniccircuit 113. In use, the capsule is delivered after a diagnostic capsuleusing an optical sensor has been passed through the intestinal tract toobtain a map of optically sensed parameters along the length of thetract. After a blockage site along the length has been determined, thecapsule 170 is ingested. Using the RF coil 175 and acoustic transducers176 a-c of the tracking system described above, the tracking systemidentifies when the capsule 170 has reached the blocked site. Thetracking system sends a telemetric control signal to the RF coil 175that instructs the controller 122 to inflate the balloon 167. Thecontroller activates valve 166 through driver 128 a which opens to allowcompressed gas from the gas source 165 to fill the chamber 168 of theballoon. The inflation of the balloon 167 expands the intestinal wall atthe site of the balloon 167 to open the blockage. The controller 122then opens the valve 169 through driver 128 b to allow the gas to escapefrom the chamber 168 through the gas exit port 172 and into theintestinal tract. The controller may release the gas upon an externaltelemetrically delivered command that is initiated by, for example, aphysician who is observing the capsule and balloon under fluoroscopy, todetermine if and when a blockage has been opened. Alternatively, theballoon may be preprogrammed to expand for a predetermined amount oftime. The expandable member may be used for a variety of diagnostic ortreatment purposes, for example, pressure sensing, opening partialblockages, measuring the openings of partially blocked or constrictedareas, providing hemostasis, delivering therapeutic substances that arecoated on the balloon 167, or affixing a capsule in an identifiedlocation to mark the location in the intestine. An expandable supportmember such as a stent may be provided on the balloon for placementwithin a stricture upon expansion of the balloon. Alternatively, thecapsule may be provided with a self-expanding support structure such asa self-expanding stent.

FIG. 10 illustrates a third embodiment of a treatment capsule of thepresent invention. Capsule 180 comprises a capsule body 181 including anelectronic circuit 113 and battery 184 coupled to the electronic circuit113. An RF coil 185 and acoustic transducers 186 a-c operate in asimilar manner as RF coil 135 and transducer 136 a-c described herein.The capsule further comprises a pump 187 filled with a dye such as,e.g., fluorescein or methylene blue to provide a surgeon withidentification of a site for surgery. Such marker may include, forexample a radiopaque marker that may be located with an active x-raysystem during a procedure, a radioactive material that may beinterrogated by a passive system, a fluorescing compound that is used toidentify the location, or a dye that stains through the wall of theintestine. The compounds may assist a surgeon in a laparoscopic or openprocedure where such imaging systems are used during the procedure orwhere visualization, e.g., of a dye or stain is possible. The pump iscoupled to a valve 189 by a conduit 188. The pump 187 and the valve 189are controlled by the controller 122 in the electronic circuitry 113through drivers 128 c and 128 d. In use, the capsule 180 is deliveredafter a diagnostic capsule having a diagnostic sensor has been passedthrough the intestinal tract to obtain a map of sensed parameters alongthe length of the tract. After a site along the length of the tract hasbeen identified for surgical intervention, the capsule 180 is ingested.Using the RF coil 185 and acoustic transducers 186 a-c of the trackingsystem described above, the tracking system identifies when the capsule180 has reached the identified site. The tracking system sends atelemetric control signal to the RF coil 185 that instructs thecontroller 122 to activate the pump 187. The controller activates thepump 187 through driver 128 c. The controller also activates valve 189through driver 128 d which opens to allow dye from the pump 187 to exitthe pump through conduit 188 and valve 189 and be sprayed onto theadjacent intestinal wall. The dye thus marks a location for surgicalintervention.

The capsule 180 may also be used to release a gas into the intestinaltract at a given location where e.g. a blockage or other anatomicalfeature is believed to exist. Using fluoroscopy, the anatomy may beobserved. Similarly, using a capsule such as capsule 180, a fluid suchas a radiopaque fluid may be released near a contriction or other areato be imaged where pump 187 pumps the fluid into the intestinal tractthrough a conduit 188 and valve 189.

FIGS. 12-14 illustrate a fourth embodiment of a treatment capsule of thepresent invention. Capsule 210 comprises a capsule body 211 including anelectrocautery ablation circuit 213, an electronic circuit 113, and abattery 214 coupled to the electronic circuit 113. The capsule 210 alsocomprises an elongate member 225 with a larger area return electrode 227located thereon. The elongate member 225 and electrodes 226, 227 areconstructed in a manner similar to elongate member 15 and electrodes 16a, 16 b, and 16 c described with respect to FIGS. 15-16 herein. A smallarea ablation electrode 226 is located on the capsule body 211,preferably in the form of a ring. A thermocouple sensor 127 d is locatedon the capsule body 211 immediately adjacent to the ablation electrode226 so that the sensor can sense the temperature of tissue that is beingtreated by the ablation electrode 226 and provide a feedback loop to anexternal controller 142 that regulates the power delivered to theablation electrode 226. An RF coil 215 and acoustic transducers 216 a-coperate in a similar manner as RF coil 135 and transducers 136 a-cdescribed herein. In this embodiment, the RF coil 215 operates at afrequency of about 1 MHz.

As illustrated in FIG. 13, the ablation electronics include, an ablationcoil 221, electrodes 226, 227, and an ablation circuit 213 including acapacitor 222. The ablation coil 221 that is tuned to a frequency ofabout 250 kHz, thus the coils 215 and 221 receive different frequencies,enabling them to distinguish between a telemetry signal and an ablationpower signal. An external variable power generator 230 (FIG. 14)supplies an RF signal at 250 kHz through power transmitter coil 231. Theablation signal received by the ablation coil 221 and parallel capacitor222 (which together form a tuned circuit to separate the ablation signalfrom the telemetry signal) is then delivered to electrodes 226, 227. Theablation electrode 226 has a considerably smaller area than the returnelectrode 227 so that the current density is greater at the ablationelectrode 226 where the ablation current is to be focused on theadjacent tissue. The thermocouple sensor 127 d provides an electricalsignal representative of the temperature of the adjacent tissue, throughthe A/D converter 126 d of the capsule circuit 113. The signal isconverted to a digital signal that is provided to the controller 122 ofthe circuit 113. The signal is telemetrically delivered to thecontroller 142 of the recorder 105 in a manner as described herein.

As illustrated in FIG. 14, the power is controlled by the controller 142of the recorder 105 which is coupled to the power generator 230 by wayof connector 233. The controller 142 in the recorder electronics 140will regulate the power output to the ablation electronics based onfeedback information as sensed by the thermocouple 127 d on the capsulebody 211 and delivered via telemetry from the capsule RF coil 215. Theregulation of the power is significant in this embodiment as the RFablation signal strength may vary with distance from the capsule, thetype of the tissue being treated, the impedance of the tissue beingtreated. Thus, the temperature feedback loop is intended to prevent overor under heating of the tissue. In addition, the treatment is initiatedby a user by activating a switch 234 coupled to the power generator 230.

In use, the tracking system is used in a manner as described above. Alocation to be treated along the length of the intestinal tract is firstidentified by a first capsule passing through the tract. Preferably thecapsule will have an optical, chemical or other means for determining alocation where bleeding is occurring. This location is identified in asubsequent pass of the ablation capsule 210 and the user turns theablation power on when the appropriate location is identified to ablateor cauterize the tissue that is bleeding. In a variation of theembodiment, a site where bleeding is present may be treated using asubsequently passed capsule having a balloon tamponade, i.e. aninflatable member that uses compression and/or a thrombogenic substancecoated on the inflatable member to help cause hemostasis. A capsuleembodiment having an inflatable member is described herein withreference to FIGS. 21 and 22.

FIGS. 15-16 illustrate a fifth embodiment of the capsule of the presentinvention. The capsule 10 comprises a treatment and sensing device thatmay be used with the tracking system. The capsule 10 is used to senseelectrical parameters of the intestinal wall and/or to treat theintestinal tract by electrically stimulating the intestinal wall. Thecapsule 10 comprises a liquid impermeable and airtight capsule body 11.The capsule body 11 contains electronic circuitry 113, battery 114, RFcoil 135 and acoustic transducers 136 a-c as described above withreference to FIGS. 3A and 3B. The capsule body 11 protects the enclosedcircuitry from body fluids while passing through the intestinal tract.The capsule body 11 is formed of a material that is compatible for usein the human body, for example, a medical grade plastic or polymer.

An elongate member 15 is affixed to an end of the capsule body 11.Electrodes 16 a, 16 b and 16 c are located on the elongate member 15.Two second, larger area electrodes 17 a and 17 b extend around the widthof the capsule body 11. Electrodes 16 a-c may be selected in a number ofcombinations to form electrode pairs to deliver stimulation to theintestinal wall (or alternatively to sense electrical activity of theintestinal wall). Additionally, one or more of electrodes 17 a and/or 17b may be utilized to work with one or more of electrodes 16 a-16 c wherecurrent density will be concentrated at the smaller electrode(s) 16 a,16 b, and/or 16 c. The capsule electronics may include logic to selectwhich electrodes should deliver stimulation pulses for optimalstimulation. The electronics may similarly control which electrodes maybe used to sense electrical activity of the intestinal wall.Alternatively, an external processing unit may determine optimalelectrode selection that is communicated to the capsule by a telemetrycommand signal.

In one preferred embodiment, the capsule 11 may be used for stimulationand subsequent measurement of electrical parameters. This function maybe used for diagnostic purposes, for example, to determine if theintestinal wall is properly conducting electrical pulses or if the wallat a particular location is an electrically hypo-active or “dead” area.In a preferred embodiment, the capsule electrodes are electricallyconfigured so that a plurality of adjacent electrode pairs can be usedwhere a first pair stimulates the intestinal wall at a first locationand the second pair then detects signals at a second location that arepropagated from the original stimulation signal. Accordingly, in avariation of one embodiment, to determine if the intestinal wall iselectrically abnormal, e.g., is electrically hypo-active, electrodes 17a and 17 b are used to deliver a stimulation signal and an electrodepair formed from at least two of electrodes 16 a-c are used to senseresulting signals propagated in an orad direction. In a variation ofanother embodiment, signal propagation in the aborad direction, i.e.,from the back of the capsule to the front assuming the front of thecapsule is oriented in a direction away from the mouth is determinedusing an electrode pair formed from at least two of electrodes 16 a-care used to deliver a stimulation signal and electrodes 17 a and 17 bsense resulting propagated signals.

As illustrated in FIG. 15, a dissolvable encasing 12 surrounds theelongate member 15, the electrodes 16 a-c, and at least a portion of thecapsule body 11. When encapsulated by the encasing 12, the elongatemember 15 is in a coiled or compressed position.

The encasing 12 is formed of a suitable dissolvable material such as,for example, a soluble gelatin or enteric coating that is dissolvable inthe body fluids contained in the intestinal tract. Such materials may beselectively dissolved based on the pH condition so that the encasing 12dissolves after the capsule 10 has passed through the highly acidicstomach and into the more neutral small intestine.

The elongate member 15 is preferably formed of a material that haselastic properties such as a Ni—Ti alloy, which permits it to becompressed into the initial configuration and to release into itselongate state when the encasing 12 has dissolved. As shown in FIG. 16,the elongate member 15 extends into its elongate form when the encasing12 has dissolved.

The capsule body 11 is provided with a front portion 11 a and a backportion 11 b of reduced diameter. The encasing 12 is bonded to the backportion 11 b by suitable means such as an adhesive. The diameter of theback portion 11 b is reduced by a sufficient amount so that thethickness of the encasing 12 forms a substantially smooth outer capsulesurface in conjunction with the outer surface of the front portion 11 aof the capsule body 11. The overall conformation of the ingestiblecapsule 11 is cylindrical in shape having a generally hemispherical endsurface 23 on the front portion 11 a and a generally hemispherical endsurface 24 on the back portion 11 b. Dissolvable encasing 12 also has agenerally hemispherical end surface 12 a.

It is desirable that the elongate flexible member 15 have an extremitywhich has a curved configuration so as to ensure that the stimulationelectrodes 16 a-c are maintained in close proximity to the wall of theintestinal tract as the capsule 10 moves through the intestinal tract ashereinafter described. The electrode 17 is formed of a conducting layerof a suitable metal such as gold deposited on the surface of the capsulebody 11. Alternatively, the additional electrodes 16 b and 16 c may becarried by additional elongate members constructed and secured to thecapsule body 11 in a similar manner as elongate member 15.

The electronic circuitry 113 shown in FIG. 4 is capable of producingvarious types of programmable waveforms. FIGS. 17A and 17B illustrateexamples of stimulation waveforms that may be used in stimulating thesmooth muscle layer of the intestinal tract. FIG. 17A illustrates awaveform design for stimulating the intestinal tract. In a preferredembodiment, the waveform 300 has a pulse amplitude of between 1 and 30mA, a pulse width of between 0.5 and 300 ms, and a frequency of aboutbetween 8 to 12 cycles per minute (this corresponds to a repetitionperiod of between 5 to 7.5 seconds). FIG. 17B illustrates an alternativewaveform design for stimulating the intestinal tract. The waveform 400utilizes bursts of pulses rather than a single pulse. The burstrepetition rate is selected, preferably, to be between about 8 to 12cycles per minute (this corresponds to a burst repetition period ofbetween 5 to 7.5 seconds). The duration of a pulse in this example isbetween about 300 .mu.s and 20 ms, and has an amplitude of about 1-30mA. The frequency of the burst pulses during a burst period are about 50to 100 Hz corresponding to a pulse repetition period of 10 to 20 ms. Theburst duration can vary from about 0.6 ms to 1 second. As is well knownto those skilled in the art, there are many different types ofelectrical stimulation programs and strategies which can be utilized forproviding electrical stimulation parameters through the circuitry 113,the principal focus being providing electrically stimulating parametersfor the intestinal tract, preferably the small intestine.

FIG. 18 illustrates a sixth embodiment of a capsule of the presentinvention. Stimulation capsule 50 is generally constructed in a similarmanner as capsule 110. Capsule 50 comprises first bipolar electrode 56and a second, electrically opposite bipolar electrode 57 on a capsulebody 51 in longitudinally spaced apart positions. The electrodes 56, 57are connected by conductors to the electronics 113 within the capsulebody 51. According to this embodiment, various electrical stimulationparameters, including those described herein, may be used.

A seventh embodiment of the capsule is shown in FIGS. 19 and 20. Capsule60 comprises a stimulation electrode deployment mechanism consisting ofa loop 76 formed of an elastic material wrapped about the capsule body61. Bipolar stimulating electrodes 66 and 67 are carried by the loop 76and are connected to the electronic circuitry 113 in the capsule body 61by conductors (not shown) extending through the hollow tubular memberforming the loop 76. As shown in FIG. 19, a dissolvable encasing 62 isprovided over the capsule body 61. This encasing 62 can be formed of thesame material as the encasing 12 in the embodiment shown in FIG. 15.When encasing 62 is dissolved, the loop 76 will expand to the ovoidlooped configuration shown in FIG. 20, bringing the stimulationelectrodes 66 and 67 into contact with the wall of the intestinal tractas the capsule 60 travels through the intestinal tract. The loop 76allows the electrodes 66, 67 to be positioned behind (orad to) thecapsule 60 regardless of its orientation in the intestinal tract. As thecapsule 60 moves through the intestinal tract the loop 76 will be incontact with the wall of the tract. The friction forces of the loop 76dragging along the wall will cause the loop 76 to shift such that theelectrodes 66, 67 are generally behind (orad to) the capsule. In thisregard, a contraction stimulated by the electrodes 66, 67 will tend toresult in forward (aborad) movement of the capsule as the stimulatedcontraction propagates along the intestinal tract.

FIGS. 21 and 22 illustrate an eighth embodiment of a capsule of thepresent invention. Capsule 80 includes an expandable member. In FIGS. 21and 22, an inflatable member with pressure sensing capabilities isillustrated. Electronic circuitry 113 is located in the capsule body 81.A pressure transducer 127 a, also located in the capsule body 81 iscoupled to circuitry 113. The pressure transducer 127 a comprises acommercially available silicone or other suitable plastic bridgepressure transducer that measures hydrostatic pressure to determinechanges in pressures as described below.

An elongate member 85 is affixed to an end of the capsule body 81.Bipolar stimulation electrodes 86, 87 are located in a spaced apartrelationship, rearwardly on the elongate member 85. Conductors 95 extendthrough the flexible elongate member 85 connecting the electrodes 86, 87to the electronics 113. Opposing ends 92 a, 92 b of an inflatableballoon 92 are mounted forwardly of the electrodes 86, 87 on theflexible elongate tubular member 85 by a suitable adhesive (not shown).A balloon inflation/deflation lumen 94 is provided in the flexibleelongate member 85 and extends from the capsule body 81 to an inflationport 93 that opens into the interior of the balloon 92 as shown in FIG.22. The balloon inflation/deflation lumen 94 is coupled to the pressuretransducer 127 a so that compression pressures sensed by the balloon 92will be supplied to the pressure transducer 127 a as the pressure of thegas in the balloon 92 and the lumen 94 changes.

The capsule 80 includes a dissolvable encasing (not shown) of the sametype as the encasing 12 shown in FIG. 15. Similar to the encasing shownin FIG. 15, such an encasing would enclose the flexible elongate member85 including the inflatable balloon 92 and electrodes 86, 87 and woulddissolve, e.g. in the small intestine releasing the elongate member 85as illustrated in FIGS. 21 and 22.

A balloon inflator is provided within the capsule 80 comprising a smallcanister 97 of compressed C0.sub.2 or other suitable gas. The canister97 is coupled to the lumen 94 through a valve connection 98. Theoperation of the valve 98 is controlled by the electronics 113 through adriver 128 a, b, c, or d. When the flexible elongate member 85 isdeployed upon dissolving of the encasing, the electronics 113 cause thevalve 98 to open and inflate the balloon 92.

Alternatively, the balloon 92 can be pre-inflated with a gas or fluidbefore enclosure within the encasing. In this case, the inflationcanister 97 and valve 98 may be eliminated. The balloon 92 is formed ofa gas impermeable material so that it will remain inflated oversubstantial periods of time. The balloon may be formed, for example, ofpolyurethane, PET, nylon or polyethylene.

In a preferred operation and use, the capsules shown in the variousembodiments in FIGS. 12 and 18-22, are used in conjunction with thecircuitry shown in FIG. 4 or FIG. 13 in small intestine electricalstimulation. A small intestine suited for treatment using the capsulemay be diseased and incapable of adequate contractile activity. Forexample the nerves of the small intestine may be compromised due togastric or diabetic neuropathy. Because of such a disorder, the patientmay have a motility disorder that would be advantageously treated usingsmall intestine electrical stimulation.

The stimulator capsule may also be used to measure other electricalcharacteristics such as EMG or impedance as described herein withrespect to the electronic circuitry 113 show in FIG. 4. A patientwishing to treat a motility disorder ingests a capsule of the presentinvention near the beginning, midway, or following the ingestion offood. A capsule when ingested will travel through the esophagus into thestomach. Where a dissolvable encasing is utilized for encapsulating theelongate member and electrode(s), the encasing is readily dissolved bythe fluids within the stomach or duodenum, permitting the flexibleelongate member carrying the stimulation electrode to be deployed.

The capsule is preferably used with the tracking system described hereinwhere treatment is triggered by an external (telemetry) signal from thetracking device. A first capsule may be delivered and an electricalparameter of the intestine may be mapped with respect to the length ofthe intestine. A second capsule may be delivered and used to provideelectrical stimulation at an identified location along the length of thetract. An external signal to the capsule signals when to begin and endstimulation.

The electrical stimulation capsule may also be used independent of thetracking system. In a variation of the embodiment, the capsule can beprogrammed to begin emitting electrical stimuli to one or morestimulation electrodes 16 a-c, and/or 17, within a predetermined timeafter ingestion, for example, within one to one and one-half hours afteringestion into the stomach, at which time it is most probable that thecapsule would have passed into the duodenum along with food materialpassing from the stomach. As an alternative, a single capsule maystimulate and measure the electrical parameters. The capsule may senseelectrical parameters and when a clinically undesirable electricalparameter is detected, the capsule may provide an appropriate electricalstimulation in. response.

Such a system would have the advantage of not requiring external gearsuch as the recorder and pods. Also, the capsule may be constructed tosense when it is in the duodenum, for example with a pH sensor or apressure sensor. Also, the electronics 113 can be triggered to commenceat the time the encasing is dissolved and the stimulation electrode isexposed to body fluids. Alternatively, electrical stimuli can betriggered by the electronics 113 to commence within a predetermined timeafter the encasing dissolves. In such case, the capsule is enclosed in agel material that dissolves after it leaves the stomach when it reachesthe small intestine. When triggered, electronic circuitry 113 initiateselectrical stimuli to the small intestine of the patient, at periodicintervals, such as, for example using one or more waveforms like thoseshown in FIGS. 17A and 17B.

Alternative electronic circuitry 313 illustrated in FIG. 23 may be usedwith any of the stimulation capsules illustrated herein. According to analternative embodiment, the electronic circuitry 313 is used in asimplified stimulation system. According to a preferred embodiment ofthe system, prior to each stimulation pulse or burst of pulses thecapsule receives basic instructions. The instructions may be a triggersignal to trigger a stimulation pulse or burst of pulses withpredetermined stimulation parameters, such as amplitude and pulse width,to be emitted by the capsule. The instructions may also includeinformation regarding the stimulation parameters for the pulses to beemitted. The instructions to trigger and/or specify a stimulation pulseor burst of pulses to be delivered to the intestinal wall aretelemetrically delivered to the electronic circuitry 313.

The electronic circuit 313 is simplified and includes a microprocessor312, ROM 315, RAM 316, a clock 311, a telemetry coil 335, a battery 314a dc-dc converter for stimulation 330, a telemetry detection circuit317, and a pacing driver 318. The microprocessor 312 is coupled to theROM 315, which contains program instructions for the microprocessor 312and any other permanently stored information that allows themicroprocessor 312 to operate. ROM 315 may also contain default andstandard stimulation parameters. The microprocessor 312 addresses memoryin a location in the ROM 315 through address bus 315 a and the ROM 315provides the stored program instructions to the microprocessor 312 viadata bus 315 b. The microprocessor is coupled to the RAM 316 via anaddress bus 316 a for addressing a location in the RAM 316 and abi-directional data bus 316 b for delivering information to and from theRAM 316. The RAM 316 may be used by the microprocessor 312 to storecustom stimulation parameters sent via telemetry prior to a series ofstimulation pulses or bursts of pulses, or, just before each stimulationpulse or burst of pulses. RAM 316 may also temporarily store anidentification code to specify the already stored default, standard orcustom stimulation parameters to be used for stimulating the intestinalwall.

The trigger signals for each stimulating pulse or burst of pulses andthe stimulation parameter instructions are supplied through thetelemetry coil 335 to the microprocessor 312 and are then deliveredthrough the pacing driver 318 in real time to the intestinal wall(through electrodes as described herein). Thus, the capsule itself doesnot direct the stimulation or the intestinal wall but receivesdirections from an external source and delivers stimulation accordinglyand in real time to the intestinal wall.

The embodiment of FIG. 23 could be further simplified by replacing themicroprocessor 312, ROM 315, RAM 316, and clock 311 with logic gates ora state machine. In such variation, some or all of the stimulationparameters may be preset and stored in the hardware in the capsule. Forexample, stimulation amplitudes could be stored as 5 different states ina simple state machine. The telemetry instruction signal could thenconsist of a simple pulse train that would represent the trigger signalas well as encode one of the five stimulation amplitudes while using anotherwise fixed stimulation pattern.

The electrical pulses provided by the electronics 113 through theelectrode pairs 16 a-c, 17 (as selected)(FIGS. 15, 16); 56, 57 (FIG.18); 66, 67 (FIGS. 19, 20); 86, 87 (FIG. 21); and 116, 117 (FIG. 3A) maybe used to create peristaltic contractions in the wall to cause movementof food material along with the capsule in the intestine. In analternative embodiment where it is desired to retard motility in thesmall intestine, inhibition of peristaltic contractions by electricalstimulation may be effected by delivering electrical pulses designed toinhibit or interfere with the inherent electrical potentials, resultingin failure of normal peristaltic contractile activity.

In certain situations with respect to motility disorders, it may bedesirable to supply synchronized stimulating pulses to the wall of thesmall intestine by the use of multiple pairs of stimulating electrodessuch as, for example, a plurality of pairs similar to electrodes 16 a-ccarried on the flexible elongate tubular member secured to the capsuleas shown in FIG. 12 and synchronizing the pulses in forward (aborad) orreverse (orad) directions in order to cause forward or reversestimulation of the intestinal tract.

As the capsule passes along the intestinal tract, it continues to supplysuccessive stimuli through the intestine. The rapidity of movement offood material through the small intestine can be controlled by thestimulating parameters such as frequency or amplitude of the signalsutilized for supplying electrical stimuli or pulses to the intestinaltract. The capsule may provide certain stimulation patterns in the smallintestine until it reaches the colon. (This may be determined by sensedelectrical or other parameters, or by a predetermined time interval). Atthis time the electrical stimuli can be terminated or alternatively theycan continue to be generated at the same or different parameters as thecapsule passes through the colon until it exits from the body throughthe rectum in a bowel movement.

Where it is necessary for the patient to ingest a capsule each time foodis ingested by the patient, the patient can have additional capsules onhand and ingest a capsule with each meal.

The electrode configuration preferably comprises two separate electricalelements forming electrically opposite bipolar electrodes. However, amonopolar or unipolar construction with a remote return is alsocontemplated by the invention. Spacing of the bipolar electrode elementsfrom one another will preferably be about 5 mm. Electrodes formed on anelongate member will preferably be constructed from a metal wire orstrip wound in a helical manner around the elongate tail portion. Theelectrode metal will preferably be corrosion resistant and biocompatiblesuch as Gold, Platinum, Titanium, etc. A helical winding pattern ispreferred to provide an electrode that is more flexible than a solidcylinder, and thereby allow the elongate tail to be more easily wound orcompressed for containment in the dissolvable portion of the capsule. Analternative construction is contemplated where the electrode is embeddedin an insulating polymer with an insulated lead extending within oralong the elongate member into the capsule body.

By varying the spacing between the stimulation electrodes or the size ofthe electrodes, it is possible to change the current density passingthrough the wall of the intestine during stimulation. A device may beprovided where electrodes may be selected to maximize these parameters.For example a plurality of electrode pairs may be provided from whichthe optimal pair of electrodes may be selected. Also individualelectrodes may be configured to form a pair of bipolar electrodes uponselection.

The electrical pulses or pulse train supplied to the stimulationelectrodes can be at suitable stimulation intervals as for example, inthe case of pacing type electrical stimulation, every few seconds up toten seconds in the small intestine or several hours in the colon.

In connection with the electrical stimulation functions describedherein, it is often desirable to measure the pressures which are createdby peristalsis of the intestinal contractions. Referring to FIGS. 21 and22, this can be readily measured by sensing the compressive forcesexerted on the balloon 92 with transducer 91. By sensing such pressuresand supplying the information by telemetry to the external recorder 105,it is possible to ascertain the efficacy of the stimulation beingapplied to the particular portion of the intestinal tract and ifnecessary to adjust the electrical stimulation parameters to create thedesired contractile forces being sensed by the balloon and the pressuretransducer. For example, if the sensed pressure indicates suboptimalcontractile response, the stimulation parameters may be adjusted, e.g.,telemetrically. If the existence of contractions is detected, thestimulation electrodes may be turned off. This may also serve toconserve battery power.

One method of use of a capsule of the present invention is in smallintestine electrical stimulation. Electronic circuitry is disposedwithin the capsule and creates electrical stimuli for causingperistaltic motion of the small intestine for causing pacing ofperistaltic motion in the small intestine. Other effects on theelectrical, chemical, and/or neural systems of the intestinal tract maybe achieved with electrical stimulation. One example includes anelectrical stimulus that is used to interfere with the naturalpacesetter potential and thus prevent organized intestinal tractcontractile activity from occurring.

The present invention provides an improved method and device fortracking an autonomous capsule as well as a method and device fortracking and diagnosing the gastrointestinal tract, preferably using atracking device. Various modifications and combinations are contemplatedby this invention and may be made without departing from the scope ofthe invention.

For example, in another embodiment of the tracking system, the directionof the ultrasound signal used for locating the capsule is reversed. Inthis embodiment, the capsule receives the ultrasound signals generatedby the pods and retransmits the signals on the RF carrier back to thepods or external monitor. In this way, the capsule position may belocated by measuring the time delay from transmission of the ultrasoundsignal(s) by the pod(s) to their reception by the capsule. Rather thanactivating all pods simultaneously, each pod may be sequentiallyactivated to transmit ultrasound. Accordingly, the pod to capsule pathis identified by the time of transmission from a particular pod. When asingle pod is activated in this way for transmission, all the remainingpods may also be switched to receive the ultrasound signal from thetransmitting pod. This allows the pod-to-pod delay times to be measured,so that the relative position of the pods can be determined on anongoing basis.

If simultaneous transmission from all pods is desired, the ultrasoundsignals from each pod may be separated by using a variety of methods.For example, each pod may generate a unique ultrasound frequencyallowing the signals to be separated by filtering.

In one variation, for example, a continuous wave signal with amplitudemodulation may be used rather than a narrower pulse. In such variation,time delays may be measured by measuring the phase of the receivedsignals relative to the transmitted signal.

Alternative reference signals may be used to establish when the acousticsignal is transmitted. For example, an infra-red link or a distributedresistive link may be used. Infra-red links may be constructed usinglight emitting diodes with an infra-red wavelength chosen to minimizedthe effects of tissue/light attenuation. The light transmitters andsensors may be on the capsule and/or at the external location for one ortwo way signal transmission. The light may be modulated with a highfrequency carrier in a similar manner to an RF link. The modulated lightsignal can then be detected after it has passed through the tissue usinga light sensor or sensors. A distributed resistive link may be used todirectly couple an electrical carrier signal through the body to anexternal sensor or sensors, or alternatively or additionally from anexternal transmitter to electrode sensors coupled to the capsule. Asmall high frequency carrier, typically 100 kHz or above, is preferablychosen for the carrier frequency to prevent any muscle stimulation bythe carrier. The sensor on the capsule or at the external location wouldthen detect the high frequency carrier signal, which would be attenuatedby the distributed resistive divider formed by the conductive bodytissue. To transmit or receive the signal to or from an externallocation, the external source or sensor would be coupled into the bodyvia two skin electrodes, spaced at some distance apart. Electrodes onthe capsule would be used to receive (or transmit) such carrier signal.The high frequency carrier would preferably be modulated in the same wayas an RF link, using amplitude, frequency or other modulation schemes asare well known in the art. Preferably, the various signals e.g., goingto or from the capsule, would be placed on different carrier frequenciesto allow for easy separation via filtering, of the outgoing and incomingsignals.

Further, as an alternative to using an externally detectable signal suchas an RF signal, as a reference signal to establish the time at whichthe acoustic pulse is emitted, the ultrasound transmitters and receiversmay be configured to establish such transmission times and thus thelocation of the capsule. Based on the differential time between twoultrasound receivers receiving an ultrasound pulse from a capsule, thepossible location of the capsule may be defined by a paraboloid planebetween the two receivers. Using more than two receivers, additionalsuch paraboloid planes representing possible locations may bedetermined. The intersection of the planes provides information fromwhich the actual location of the capsule may be derived. By filteringout impossible locations (e.g., by knowing points that would lie outsidea patient's body, e.g., based on pod placement on a patient, or byadding additional pods for additional location information), the actuallocation of the capsule may be determined.

According to one variation, the differential distance is determined bymultiplying the differential time between the reception of theultrasound signal at one pod and the reception at the other pod timesthe speed of sound in tissue. The possible location of the capsule basedon the derived differential distance is represented by a paraboloidplane between the two pods. When a third acoustic reference receiver isadded, the detected differential time between receiver one and three andthe differential time between receivers two and three provide additionalparaboloid planes of possible capsule locations. Two paraboloid planesintersect in a paraboloid or ellipsoid line; intersection with a thirdparaboloid plane defines one or more points of possible capsulelocations. Strategic positioning of the acoustic reference receivers,use of additional receivers and/or exclusion of invalid mathematicalsolutions (e.g. outside of the patient's body) may enable a singlesolution to be obtained for capsule location.

The foregoing embodiments and variations of the invention areillustrative and not contemplated to be limiting, having been presentedby way of example. Numerous other variations and embodiments, as wouldbe apparent to one of ordinary skill in the art, are contemplated asfalling within the scope of the invention as defined by the claims andequivalents thereof.

The invention claimed is:
 1. A system for the delivery of a drug to agastrointestinal tract, the system comprising: a capsule sized to passthrough an intestinal tract of a patient; an acoustic transmittercoupled to the capsule, the acoustic transmitter configured to transmitan acoustic tracking signal between the capsule and a location externalto a patient's body to track a linear position of the capsule within thepatient's intestinal tract as the capsule is passing through theintestinal tract; a reference signal generator coupled to the capsule,the reference signal generator configured to generate and transmit areference signal for identifying a time of tracking signal origination;a drug delivery device configured to deliver drug to the intestinaltract; and a controller configured to actuate the drug delivery deviceas the capsule is passing through the intestinal tract at a desiredposition in the intestinal tract based on the capsule position withinthe intestinal tract.
 2. The system of claim 1 wherein the drug deliverydevice comprises a pump.
 3. The system of claim 1, wherein the drugdelivery device comprises a valve or a solenoid.
 4. The system of claim1, wherein the controller is actuable responsive to an external signal.5. The system of claim 4, wherein the drug delivery device includes anRF receiver for receiving the external signal, the RF receiver operablycoupled to at least one of the controller or the drug delivery device.6. The system of claim 4, wherein the controller actuates the drugdelivery device responsive to the external signal.
 7. The system ofclaim 6, wherein the controller includes programming for actuating thedrug delivery device responsive to the external signal.
 8. The system ofclaim 1, further comprising: a sensor for sensing a condition of theintestinal tract, the sensor operably coupled to at least one of thecontroller or the drug delivery device.
 9. The system of claim 8,wherein the sensor comprises a pressure sensor, a strain gauge, or a pHsensor.
 10. The system of claim 8, wherein the drug delivery device isactuatable responsive to the sensed condition of the intestinal tract.11. The system of claim 10, wherein the controller actuates the drugdelivery device responsive to the sensed condition of the intestinaltract.
 12. The system of claim 11, wherein the controller includesprogramming for actuating the drug delivery device responsive to thesensed condition.
 13. The system of claim 1, wherein the capsuleincludes the drug.
 14. The system of claim 1, further comprising: aplurality of acoustic transducers configured to receive the trackingsignal.
 15. The system of claim 14, wherein the plurality of acoustictransducers comprise at least three acoustic transducers.
 16. The systemof claim 14, wherein the plurality of acoustic transducers are arrangedin a cartesian coordinate system.
 17. The system of claim 14, whereinthe plurality of acoustic transducers are configured to receive andtransmit signals between each other.
 18. The system of claim 14, whereinthe plurality of acoustic transducers are adhereably positioned on thepatient's skin.
 19. The system of claim 14, wherein at least one of theplurality of acoustic transducers also includes an RF device forreceiving and/or sending signals to the capsule.
 20. The system of claim14, further comprising: a patient wearable recorder device coupled tothe plurality of acoustical transducers, the recorder device configuredto record output from the plurality of acoustical transducers.